R. Frank Cook, PhD

Maxwell H. Gluck Equine Research Center
Department of Veterinary Science
University of Kentucky Lexington, Kentucky 40546-0099

At present much of my research is focused on Equine Infectious Anemia Virus (EIAV) a lentivirus closely related to Human Immunodeficiency Virus (HIV) that has the capability to infect all members of the horse family. Although EIAV does not induce chronic immunodeficiency, infection with some strains can result in death while others may produce severe recurring bouts of disease characterized by high fever, thrombocytopenia, weight loss and anemia.

Lentiviruses have evolved numerous sophisticated strategies to evade elimination by host immune responses and so infections are for life. However in many cases the equine immune system eventually “learns” to control viral replication keeping the EIAV burden below the threshold levels required to cause disease and creating a long-term inapparent carrier.

Much of my past research at the Gluck Center has involved the production of chimeric infectious molecular clones to identify genetic determinants of pathogenesis associated with certain virulent EIAV strains. Furthermore we have produced a different series of infectious molecular clones by site-directed mutagenesis techniques to characterize amino acid residues that confer generalized resistance to neutralizing antibodies. This is a survival trait employed by EIAV and other lentiviruses to ensure that neutralization only occurs in the presence of very high concentrations of antibody.

My most recent research interests are in the field of vaccine design. Vaccines are generally successful when they duplicate natural fully protective immune responses induced by an infection. Unfortunately, natural immune responses are only partially protective against lentiviruses suggesting that to be completely effective EIAV vaccines will need to stimulate responses that exceed the normal repertoire. However such extraordinary responses may be achievable by combining some of the powerful immunostimulatory equine cytokines that have recently become available with novel presentation of viral antigens made possible by the inherent flexibility of genetic immunization techniques.

In addition to EIAV research I intend to capitalize on previous experience in genetic engineering to develop viral and non-viral gene delivery systems for the transient expression of specific immunoregulatory genes within the equine lung for treatment of inflammatory airway disease.